Unit 16: Macrocytic anemias Flashcards
What is the main cause of megaloblastic anemia?
Impaired DNA synthesis; reduction in the number of cell divisions
When B12 or folate is deficient, the production of what nucleotide is impaired?
Thymidine
Which deficiency has more of a direct affect, folate or B12?
Folate, in preventing the methylation of dUMP
Which deficiency has more of an indirect affect, folate of B12?
B12, preventing the production of THF from 5-methyl THF
If there is no B12, what happens to the inactive folate that needs to be converted?
It is stuck in its inactive form, aka the folate trap
Where is 5-methyl THF converted into THF?
The cytoplasm
What happens to 5-methyl THF if it is not readily polyglutamated in the cell?
It will leak out of the cell, decreasing the intracellular folate
What happens to homocysteine in the case of B12 or folate deficiency?
It accumulates because methionine synthase is unable to convert it to methionine without vitamin B12 as a cofactor
What happens to the DNA in the case of a thymidine deficiency?
Uracil is incorporated into the DNA strand instead and is then removed in the replicated strand. This causes many single strand breaks
What is the term for abnormal blood cell development?
Ineffective hematopoiesis
What happens to most of the early erythroid progenitors and precursors in megaloblastic anemia?
They are destroyed when devision is halted via cell lysis or apoptosis
What happens to the abnormal cells that do make it to the peripheral blood stream in megalobastic anemia?
They are increased in size, macrocytic
Can RNA synthesis occur without thymidine?
Yes, it needs uracil instead
As a result of RNA synthesis occurring and DNA synthesis halting, what happens to the cytoplasm development?
Cytoplasm is able to develop normally, in asynchrony with the nuclear development
What is pancytopenia?
Ineffective hematopoiesis of all 3 blood cell lineages
What are the general symptoms of anemia?
Fatigue, shortness of breath, and weakness
What are some of the neurologic manifestations of B12 deficiency?
Memory loss, numbness, tingling, loss of balance
What are some of the neuropsychiatric manifestations of B12 deficiency?
Personality changes and psychosis
What are some of the specific manifestations of folate deficiency?
Depression, peripheral neuropathy, psychosis and neural tube defects (i.e. spina bifida)
What is the most common cause of folate deficiency?
Inadequate intake
What is the most common cause of B12 deficiency?
Impaired absorption
What are the 5 causes of impaired absorption of B12?
Failure to separate, lack of intrinsic factor, malabsorption, inherited factors and competition
What is it called to have a loss of epithelial cells on the tongue, resulting in a smooth surface and soreness?
Glossitis
Which one takes longer to develop symptoms for, B12 deficiency or folate deficiency?
B12 - up to a few years, folate - up to a few months (this reflects the storage capacity of each vitamin)
What is steatorrhea?
Fat in the feces
What intestinal diseases may cause impaired absorption of folate?
Sprue and celiac disease
Is folate heat labile or heat stable?
Labile
Is B12 heat labile or heat stable?
Stable
Binding carrier for B12 in the stomach?
Haptocorrin
Binding carrier for B12 in the small intestine?
Intrinsic factor
Binding carrier for B12 in enterocyte?
Transcobalamin
What autoimmune disease is the result of lack of intrinsic factor?
Pernicious anemia
What are two examples of competition for B12?
Fish tapeworm, and blind loops (portions of the intestine that are stenotic as a result of surgery and have an overgrowth of competing intestinal bacteria)
What disease may cause a failure to separate B12 from haptocorrin due to the lack of gastric acidity or trypsin?
Chronic pancreatic disease
What does H. pylori do to cause a lack of intrinsic factor?
Destroys parietal cells of the stomach and intestines
What is achlorhydria?
A lack of hydrochloric acid in the gastric digestive fluids
What are the most indicative clues of megaloblastic anemia from a blood smear?
Dacrocytes, oval macrocytes, hypersegmented neutophils and possibly Howell-Jolly bodies, occasional pronormoblasts
Why is the MCHC usually within normal range for megaloblastic anemia?
Because the hgb production is not affected
Why is the MCV usually high for megaloblastic anemia?
Because of the increase volume of the cells
Is the retic count elevated for megaloblastic anemia?
No
Is the RDW elevated for megaloblastic anemia?
Yes
What happens to the H and H levels in megaloblastic anemia?
They are decreased
When is a bone marrow exam done for megaloblastic anemia?
To confirm hypercellular marrow when there is pancytopenia in the blood
What will you see in bone marrow exam for a patient with megaloblasic anemia?
Large banded neutrophils, many large immature blast cells and nuclear-cytoplasm asynchrony
What happens to methylmalonic acid levels when B12 levels decrease? Why does this happen?
It increases due to the fact that B12 is a cofactor needed to convert methylmalonyl CoA to succinyl CoA (some of the accumulated methylmonyl CoA is hydrolyzed to methylmalonic acid)
What happens to the levels of homocysteine when folate or B12 are decreased?
It is increased
What sort of test is done to diagnose pernicious anemia?
Antibody assay to detect the development of antibodies to intrinsic and parietal cells
When is a stool analysis done for B12 deficiency?
To detect the presence of D. latum (hookworm)
What are the nonmegaloblastic macrocytic anemias?
Liver disease, chronic alcoholism and bone marrow failure (or aplastic anemia)
Are retics increased in a patient with nonmegaloblastic macrocytic anemia?
Yes!
Do you see hypersegmented neutrophils and oval macrocytes in nonmegaloblastic macrocytic anemia?
No
